Elevated Serum Anti-Saccharomyces cerevisiae, Anti-I2 and Anti-OmpW Antibody Levels in Patients with Suspicion of Celiac Disease
- 141 Downloads
Expression of anti-Saccharomyces cerevisiae antibodies (ASCA) identifies patients and individuals at risk for Crohn’s disease and has also been reported in 40–60% of celiac disease (CD) cases, suggesting a role of host response to enteric microbiota in the development of inflammatory lesions. In this prospective study in patients with suspicion of CD, we evaluate the frequency and association of ASCA to serological responses for other host microbial targets formally associated with Crohn’s disease, including the Pseudomonas fluorescens associated sequence I2 and a Bacteroides caccae TonB-linked outer membrane protein, OmpW.
Small bowel mucosal biopsies were taken from 242 patients with suspicion of CD, their sera were tested for antibodies to tissue transglutaminase (tTG), ASCA, I2, and OmpW. Eighty adult healthy blood donors were used as controls.
The diagnosis of CD was confirmed on biopsy in 134 cases. The occurrence of ASCA and I2 positivity was significantly higher in adult CD patients than in patients with non-CD disease. Anti-I2 levels in the sera were significantly higher in adult CD patients than in non-CD disease or the controls and anti-OmpW levels in CD and non-CD patients when compared to controls. Positive seroreactivity to OmpW seemed to increase with age. Of the CD patients, 90% were seropositive for at least one microbial antigen tested.
This study demonstrates a mosaic of disease-related serological responses to microbial antigens in patients with CD. Immune responses to commensal enteric bacteria may play a role in the small intestine mucosal damage in CD.
KeywordsTissue transglutaminase I2 OmpW ASCA serology celiac disease
This study was supported by grants from the Paediatric Research Foundation, the Competitive Research Funding of the Pirkanmaa Hospital District, the Finnish Gastroenterology Association (MA), the Mary and Georg C Ehrnrooth Foundation and, and NIH PO1-DK 46763 (J.B.). We would like to thank Leena Ripsaluoma, Marja-Leena Koskinen, and Mikko Hurme for excellent assistance in preparing this study
- 1.Walker-Smith JA, Guandalini S, Schmitz J, et al. Revised criteria for diagnosis of coeliac disease. Arch Dis Child. 1990;65:909–11.Google Scholar
- 6.Salmi TT, Collin P, Maki M, Laurila K, Partanen J, Huhtala H, Király R, Lorand L, Reunala T, Mäki M, Kaukinen K. Immunoglobulin a autoantibodies against transglutaminase 2 in the small intestinal mucosa predict forthcoming celiac disease. Aliment Pharmacol Ther. 2006 1;24:541–52.PubMedCrossRefGoogle Scholar
- 15.Damoiseaux J, Bouten B, Linders A, Austen J, Roozendaal C, Russel MG, Forget PP, Tervaert JW. Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies for inflammatory bowel disease: high prevalence in patients with celiac disease. J Clin Immunol. 2002;22(5):281–8. Sep.PubMedCrossRefGoogle Scholar
- 16.Granito A, Zauli D, Muratori P, Muratori L, Grassi A, Bortolotti R, Petrolini N, Veronesi L, Gionchetti P, Bianchi FB, Volta U. Anti-Saccharomyces cerevisiae and perinuclear antineutrophil cytoplasmic antibodies in coeliac disease before and after gluten-free diet. Aliment Pharmacol Ther. 2005;21:881–7.PubMedCrossRefGoogle Scholar
- 18.Rioux JD, Daly MJ, Silverberg MS, Steinhart AH, McLeod RS, Griffiths AM, Green T, Brettin TS, Stone V, Bull SB, Bitton A, Williams CN, Greenberg GR, Cohen Z, Lander ES, Hudson TJ, Siminovitch KA. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet. 2001;29:223–8. Oct.PubMedCrossRefGoogle Scholar
- 19.Amundsen SS, Adamovic S, Hellqvist A, Nilsson S, Gudjónsdóttir AH, Ascher H, Ek J, Larsson K, Wahlström J, Lie BA, Sollid LM, Naluai AT: A comprehensive screen for SNP associations on chromosome region 5q31–33 in Swedish/Norwegian celiac disease families. Eur J Hum Genet. 2007;15:980–7.Google Scholar
- 26.Papp M, Altorjay I, Norman GL, Shums Z, Palatka K, Vitalis Z, Foldi I, Lakos G, Tumpek J, Udvardy ML, Harsfalvi J, Fischer S, Lakatos L, Kovacs A, Bene L, Molnar T, Tulassay Z, Miheller Veres G, Papp J, Lakatos PL, Hungarian IBD Study Group. Seroreactivity to microbial components in Crohn’s disease is associated with ileal involvement, noninflammatory disease behavior and NOD2/CARD15 genotype, but not with risk for surgery in a Hungarian cohort of IBD patients. Inflamm Bowel Dis. 2007;13:984–92.PubMedCrossRefGoogle Scholar
- 36.Desplat-Jego S, Johanet C, Escande A, Goetz J, Fabien N, Olsson N, Ballot E, Sarles J, Baudon JJ, Grimaud JC, Veyrac M, Chamouard P, Humbel RL. Update on Anti-Saccharomyces cerevisiae antibodies, anti-nuclear associated anti-neutrophil antibodies and antibodies to exocrine pancreas detected by indirect immunofluorescence as biomarkers in chronic inflammatory bowel diseases, Results of a multicenter study. World J Gastroenterol. 2007;13(16):2312–8. Apr 28.PubMedGoogle Scholar
- 40.Drago S, El Asmar R, Di Pierro M, Grazia Clemente M, Tripathi A, Sapone A, Thakar M, Iacono G, Carroccio A, D’Agate C, Not T, Zampini L, Catassi C, Fasano A. Gliadin, zonulin and gut permeability: effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006;41:408–19.PubMedCrossRefGoogle Scholar
- 49.Dubinsky MC, Lin YC, Dutridge D, Picornell Y, Landers CJ, Farrior S, Wrobel I, Quiros A, Vasiliauskas EA, Grill B, Israel D, Bahar R, Christie D, Wahbeh G, Silber G, Dallazadeh S, Shah P, Thomas D, Kelts D, Hershberg RM, Elson CO, Targan SR, Taylor KD, Rotter JI, Yang H, Western Regional Pediatric IBD Research Alliance. : Serum immune responses predict rapid disease progression among children with Crohn’s disease: immune responses predict disease progression. Am J Gastroenterol. 2006;101:360–7.PubMedCrossRefGoogle Scholar
- 51.Ferrante M, Henckaerts L, Joossens M, Pierik M, Joossens S, Dotan N, Norman GL, Altstock RT, Van Steen K, Rutgeerts P, Van Assche G, Vermeire S. New serological markers in inflammatory bowel disease are associated with complicated disease behaviour. Gut. 2007;56:1394–403.PubMedCrossRefGoogle Scholar